AUTHOR=Perez-Zsolt Daniel , Cantero-Pérez Jon , Erkizia Itziar , Benet Susana , Pino Maria , Serra-Peinado Carla , Hernández-Gallego Alba , Castellví Josep , Tapia Gustavo , Arnau-Saz Vicent , Garrido Julio , Tarrats Antoni , Buzón Maria J. , Martinez-Picado Javier , Izquierdo-Useros Nuria , Genescà Meritxell TITLE=Dendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1 JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00825 DOI=10.3389/fimmu.2019.00825 ISSN=1664-3224 ABSTRACT=

Antigen presenting cells from the cervical mucosa are thought to amplify incoming HIV-1 and spread infection systemically without being productively infected. Yet, the molecular mechanism at the cervical mucosa underlying this viral transmission pathway remains unknown. Here we identified a subset of HLA-DR+ CD14+ CD11c+ cervical DCs at the lamina propria of the ectocervix and the endocervix that expressed the type-I interferon inducible lectin Siglec-1 (CD169), which promoted viral uptake. In the cervical biopsy of a viremic HIV-1+ patient, Siglec-1+ cells harbored HIV-1-containing compartments, demonstrating that in vivo, these cells trap viruses. Ex vivo, a type-I interferon antiviral environment enhanced viral capture and trans-infection via Siglec-1. Nonetheless, HIV-1 transfer via cervical DCs was effectively prevented with antibodies against Siglec-1. Our findings contribute to decipher how cervical DCs may boost HIV-1 replication and promote systemic viral spread from the cervical mucosa, and highlight the importance of including inhibitors against Siglec-1 in microbicidal strategies.